lithium
Mood stabilizer· Brands: Camcolit, Priadel, Liskonum, Lithobid, EskalithPO
Mechanism of action
Lithium modulates neurotransmitter release and signalling in the brain. It inhibits inositol monophosphatase, reducing inositol recycling and affecting phosphatidylinositol second messenger systems. It also influences sodium and calcium ion transport across cell membranes, and may alter gene expression and neuroplasticity. These effects are thought to stabilise mood and reduce manic episodes.
Pharmacokinetics
Lithium is well absorbed from the gastrointestinal tract with peak plasma concentrations 1 to 3 hours after oral administration. It is not protein bound and distributes throughout total body water. Lithium is not metabolised and is excreted almost entirely by the kidneys, with 95% of a dose appearing in urine. Elimination half-life is about 24 hours, but may be prolonged in older adults and in renal impairment. Excretion is affected by sodium balance: sodium depletion decreases lithium clearance.
Indications & dosing
Acute mania
Titrate to serum lithium 0.8-1.2 mmol/L.
- adult · PO: 600–900 mg divided doses · Titrate to serum lithium 0.8-1.2 mmol/L.
Bipolar depression
Target serum lithium 0.6-0.8 mmol/L.
- adult · PO: 600–1200 mg divided doses · Target serum lithium 0.6-0.8 mmol/L.
Maintenance treatment of bipolar disorder
Target serum lithium 0.6-0.8 mmol/L.
- adult · PO: 600–1200 mg divided doses · Target serum lithium 0.6-0.8 mmol/L.
Adjunct for treatment-resistant depressionoff-label
Off-label; target serum lithium 0.4-0.6 mmol/L.
- adult · PO: 300–600 mg divided doses · Off-label; target serum lithium 0.4-0.6 mmol/L.
Contraindications & precautions
- Severe renal impairment · Lithium is excreted by the kidneys; accumulation can cause toxicity. Consider alternative mood stabilizer.
- Untreated hypothyroidism · Lithium can worsen thyroid function; treat and monitor thyroid levels if used.
- Pregnancy · Teratogenic risk, especially in the first trimester. Use only if benefits outweigh risks with appropriate monitoring.
- Breastfeeding · Lithium is excreted in breast milk; monitor infant serum levels and for signs of toxicity.
- Monitor serum lithium levels regularly; the therapeutic range is typically 0.4 to 1.0 mmol/L.
- Maintain adequate hydration and a consistent sodium intake; avoid dehydration and salt restriction.
- Use caution with drugs that reduce lithium clearance, such as ACE inhibitors, angiotensin receptor blockers, NSAIDs, and diuretics.
- Monitor renal and thyroid function at baseline and periodically during treatment.
- Educate patients to recognise signs of lithium toxicity (coarse tremor, confusion, ataxia, vomiting) and seek medical advice promptly.
- Consider ECG monitoring in patients with pre-existing cardiac disease or significant cardiovascular risk.
Adverse effects
- Polyuria
- Polydipsia
- Fine tremor
- Weight gain
- Hypothyroidismserious
- Nephrogenic diabetes insipidusserious
- Lithium toxicityserious
- Cardiac arrhythmiasserious
Interactions
- ibuprofenmajorAvoid concurrent use where possible, particularly in patients with pre-existing renal impairment or those receiving long-term lithium therapy. If ibuprofen is necessary, use the lowest effective dose for the shortest duration. Monitor serum lithium levels at baseline, then after 3 to 7 days of starting ibuprofen, and periodically thereafter. Monitor renal function (creatinine, eGFR) and signs of toxicity. Adjust lithium dose as needed and recheck levels after any change.
- furosemidemajorAdvise the patient to maintain adequate fluid and sodium intake. Avoid thiazides if possible, as they reduce lithium clearance even more than loop diuretics; if an alternative diuretic is needed, use one with minimal effect on lithium handling and monitor levels closely.
- lisinoprilmajorAvoid co-prescription where possible. If an ACE inhibitor is necessary, consider an alternative antihypertensive. If combined, use the lowest effective doses, monitor serum lithium levels and renal function at baseline, after any dose change, and at least weekly for the first few weeks, then less frequently. Patients should be advised to seek immediate medical attention if symptoms of lithium toxicity occur.
- hydrochlorothiazidemajorAvoid the combination if possible. If unavoidable, reduce the lithium dose and monitor serum lithium levels closely, especially after starting or stopping the thiazide. Consider using an alternative diuretic that has less effect on lithium clearance.
- diclofenacmajorAvoid concurrent use if alternatives exist. If co-prescription is necessary, monitor serum lithium levels closely before and during therapy, and after stopping diclofenac. Adjust lithium dose based on levels. Monitor renal function and watch for signs of toxicity. Consider a non-NSAID analgesic such as paracetamol if appropriate. Advise patients to seek medical attention if symptoms develop.
- bendroflumethiazidemajorAvoid this combination if possible. If co-prescription is necessary, monitor serum lithium levels frequently, for example every 3 to 5 days initially and then weekly until stable. Reduce the lithium dose as needed and monitor for signs of toxicity, including neurological and gastrointestinal symptoms. Advise the patient to maintain adequate fluid intake and to seek medical attention if symptoms develop. Consider alternative diuretics, such as loop diuretics, which have a smaller effect on lithium clearance, but regular monitoring is still advised.
- naproxenmajorAvoid co-prescription if possible; consider alternative analgesics such as paracetamol or aspirin. If combined treatment is necessary, monitor serum lithium concentrations closely at baseline, after 3 to 5 days of starting naproxen, and weekly thereafter. Monitor for signs of lithium toxicity and adjust the lithium dose accordingly. Educate the patient about symptoms of toxicity.
Renal & hepatic adjustment
- eGFR 0–30: Avoid. Consider alternative mood stabiliser. Lithium is renally cleared; severe impairment risks accumulation and toxicity. (avoid)
- eGFR 30–60: Reduce dose by approximately 50% and monitor serum lithium levels closely. May require extended dosing interval.
- eGFR 60–90: Use standard dose with caution. Monitor lithium levels and renal function more frequently.
- eGFR 90+: Standard dose is appropriate. Monitor lithium levels periodically (every 3-6 months) and renal function annually.
Monitoring, pregnancy & toxicity
- Serum lithium concentration · 12 hours after last dose, then every 3-6 months once stable
- Serum creatinine and eGFR · Every 6 months; more frequently with renal impairment
- Thyroid function (TSH, free T4) · Every 6-12 months
- Serum calcium · Periodically; lithium affects calcium metabolism
- Weight · At baseline and periodically
- Pregnancy: Lithium is associated with a small increased risk of congenital cardiac anomalies, including Ebstein anomaly, particularly with exposure during the first trimester. However, sudden discontinuation carries a high risk of affective relapse. Therefore, if the patient is stable on lithium, it is often continued at the lowest effective dose, with foetal echocardiography at 16-20 weeks. The decision should involve the specialist and patient, weighing risks and benefits. If possible, consider alternative agents; if lithium is used, ensure therapeutic drug monitoring and multidisciplinary care.
- Toxicity: Gastrointestinal: nausea, vomiting, diarrhoea · Stop lithium; measure serum lithium level; supportive care with fluids and electrolytes; consider activated charcoal if recent ingestion.
- Toxicity: Neurological: coarse tremor, ataxia, confusion, seizures · Stop lithium; hospital admission; monitor serum lithium level; consider haemodialysis in severe cases.
- Toxicity: Cardiac: arrhythmias, bradycardia, conduction defects · Stop lithium; 12-lead ECG and continuous cardiac monitoring; treat arrhythmias; consider haemodialysis.
- Toxicity: Renal: nephrogenic diabetes insipidus, acute kidney injury · Stop lithium; monitor electrolytes and fluid balance; rehydrate; consider lithium level and haemodialysis if severe.
Clinical notes
Lithium has a narrow therapeutic index; serum levels must be monitored regularly, typically aiming for 0.6 to 1.0 mmol/L for maintenance therapy. Levels above 1.5 mmol/L indicate toxicity with symptoms including coarse tremor, ataxia, confusion, and seizures. Common side effects include fine tremor, polyuria, polydipsia, and weight gain. Long-term use may cause hypothyroidism and renal impairment, so thyroid and kidney function should be checked periodically. Lithium interacts with NSAIDs, ACE inhibitors, and diuretics, which can increase serum levels. Prescribing requires careful patient education and frequent monitoring. Always consult local formulary and prescribing information.
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BNF; local formulary